Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

Jin Ye; Isabel A. Calvo; Itziar Cenzano; Amaia Vilas; Xabier Martinez-de-Morentin; Miren Lasaga; Diego Alignani; Bruno Paiva; Ana C. Viñado; Patxi San Martin-Uriz; Juan P. Romero; Delia Quilez Agreda; Marta Miñana Barrios; Ignacio Sancho-González; Gabriele Todisco; Luca Malcovati; Nuria Planell; Borja Saez; Jesper N. Tegner; Felipe Prosper; David Gomez-Cabrero

doi:10.1016/j.isci.2022.104225

Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

Jin Ye, Isabel A. Calvo, Itziar Cenzano, Amaia Vilas, Xabier Martinez-de-Morentin, Miren Lasaga, Diego Alignani, Bruno Paiva, Ana C. Viñado, Patxi San Martin-Uriz, Juan P. Romero, Delia Quilez Agreda, Marta Miñana Barrios, Ignacio Sancho-González, Gabriele Todisco, Luca Malcovati, Nuria Planell, Borja Saez^*, Jesper N. Tegner^*, Felipe Prosper^*David Gomez-Cabrero^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.

Original language	English (US)
Article number	104225
Journal	iScience
Volume	25
Issue number	5
DOIs	https://doi.org/10.1016/j.isci.2022.104225
State	Published - May 20 2022

Bibliographical note

Funding Information:
This research was funded by grants from The Spanish Government , through project PID2019-111192GA-I00 ( MICINN ) to DGC. Instituto de Salud Carlos III ( ISCIII ) and co-financed by FEDER : PI16/02024 , PI17/00701 and PI19/01352 , TRANSCAN EPICA AC16/00041 , CIBERONC CB16/12/00489 ; Redes de Investigación Cooperativa (TERCEL RD16/0011/0005 ); Spanish Ministry of Economy, Industry and Competitivity ( RTHALMY SAF2017-92632-EXP ); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Económico y Empresarial ( AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013 ). The study was also supported by Cancer Research UK [ C355/A26819 ] and Cancer Research UK , FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation ( Brian van Novis ), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III ( ISCIII ) ( PI17/01346 and PI20/00152 ), co-funded by the ERDF (A way to make Europe); FC-AECC ( AIO16163636SAEZ ); Gobierno de Navarra ( 0011-3638-2020-000011 ) co-funded by the ERDF through the Operative Program 2014–2020 of Navarra and Gobierno de Navarra ( 0011-3597-2020-000005 ) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovación y Universidades , Gobierno de España , Sara Borrell award from Instituto de Salud Carlos III ( ISCIII ) and Marie Curie grant ( H2020-MSCA-IF-837491 ) from European Commission . ICA was supported by AECC predoctoral fellowship . NP was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovación y Universidades , Gobierno de España ( FJC2019-042304-I ). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK , FCAECC and AIRC Accelerator Award Program (Project # C355/A26819 and # 22796 ).

Funding Information:
We would like to thank the staff of the flow cytometry core, the advances genomic lab, and the animal facility at CIMA Universidad de Navarra for their invaluable technical and intellectual assistance. We are particularly grateful to the healthy volunteers who donated bone marrow tissue for this study. We also acknowledge Ali O. Balubaid's help in writing. We would like to acknowledge Miguel Cocera-Fernandez's contribution to the Graphical Abstract. This research was funded by grants from The Spanish Government, through project PID2019-111192GA-I00 (MICINN) to DGC. Instituto de Salud Carlos III (ISCIII) and co-financed by FEDER: PI16/02024, PI17/00701 and PI19/01352, TRANSCAN EPICA AC16/00041, CIBERONC CB16/12/00489; Redes de Investigaci?n Cooperativa (TERCEL RD16/0011/0005); Spanish Ministry of Economy, Industry and Competitivity (RTHALMY SAF2017-92632-EXP); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Econ?mico y Empresarial (AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013). The study was also supported by Cancer Research UK [C355/A26819] and Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation (Brian van Novis), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III (ISCIII) (PI17/01346 and PI20/00152), co-funded by the ERDF (A way to make Europe); FC-AECC (AIO16163636SAEZ); Gobierno de Navarra (0011-3638-2020-000011) co-funded by the ERDF through the Operative Program 2014?2020 of Navarra and Gobierno de Navarra (0011-3597-2020-000005) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a, Sara Borrell award from Instituto de Salud Carlos III (ISCIII) and Marie Curie grant (H2020-MSCA-IF-837491) from European Commission. ICA was supported by AECC predoctoral fellowship. NP was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a (FJC2019-042304-I). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK, FCAECC and AIRC Accelerator Award Program (Project #C355/A26819 and #22796). B.S. J.T. F.P. and D.G.C. conceived and directed the research project. I.A.C. and B.S. designed the research experiments. I.A.C. with help from I.C. performed the isolation and FACS sorting of BM cells. J.Y. performed all the computational experiments, and analyzed the data with help from X.M.M. M.L. and N.P. A.V. performed the scRNA-Seq experiments. B.S. and D.G.C. supervised the work. All authors actively participated in the discussions underlying this manuscript. I.A.C. I.C. J.Y. B.S. and D.G.C. discussed the results and wrote the final manuscript with input from J.T. and F.P. All authors contributed to, read and approved the final manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2022 The Authors

Keywords

Biological sciences
Omics
Stem cells research
Transcriptomics

ASJC Scopus subject areas

General

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10.1016/j.isci.2022.104225

Cite this

Ye, J., Calvo, I. A., Cenzano, I., Vilas, A., Martinez-de-Morentin, X., Lasaga, M., Alignani, D., Paiva, B., Viñado, A. C., San Martin-Uriz, P., Romero, J. P., Quilez Agreda, D., Miñana Barrios, M., Sancho-González, I., Todisco, G., Malcovati, L., Planell, N., Saez, B., Tegner, J. N., ... Gomez-Cabrero, D. (2022). Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation. iScience, 25(5), Article 104225. https://doi.org/10.1016/j.isci.2022.104225

@article{9ec6eb8f837e4118b8013964e28c5664,

title = "Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation",

abstract = "Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.",

keywords = "Biological sciences, Omics, Stem cells research, Transcriptomics",

author = "Jin Ye and Calvo, {Isabel A.} and Itziar Cenzano and Amaia Vilas and Xabier Martinez-de-Morentin and Miren Lasaga and Diego Alignani and Bruno Paiva and Vi{\~n}ado, {Ana C.} and {San Martin-Uriz}, Patxi and Romero, {Juan P.} and {Quilez Agreda}, Delia and {Mi{\~n}ana Barrios}, Marta and Ignacio Sancho-Gonz{\'a}lez and Gabriele Todisco and Luca Malcovati and Nuria Planell and Borja Saez and Tegner, {Jesper N.} and Felipe Prosper and David Gomez-Cabrero",

note = "Funding Information: This research was funded by grants from The Spanish Government , through project PID2019-111192GA-I00 ( MICINN ) to DGC. Instituto de Salud Carlos III ( ISCIII ) and co-financed by FEDER : PI16/02024 , PI17/00701 and PI19/01352 , TRANSCAN EPICA AC16/00041 , CIBERONC CB16/12/00489 ; Redes de Investigaci{\'o}n Cooperativa (TERCEL RD16/0011/0005 ); Spanish Ministry of Economy, Industry and Competitivity ( RTHALMY SAF2017-92632-EXP ); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Econ{\'o}mico y Empresarial ( AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013 ). The study was also supported by Cancer Research UK [ C355/A26819 ] and Cancer Research UK , FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation ( Brian van Novis ), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III ( ISCIII ) ( PI17/01346 and PI20/00152 ), co-funded by the ERDF (A way to make Europe); FC-AECC ( AIO16163636SAEZ ); Gobierno de Navarra ( 0011-3638-2020-000011 ) co-funded by the ERDF through the Operative Program 2014–2020 of Navarra and Gobierno de Navarra ( 0011-3597-2020-000005 ) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovaci{\'o}n y Universidades , Gobierno de Espa{\~n}a , Sara Borrell award from Instituto de Salud Carlos III ( ISCIII ) and Marie Curie grant ( H2020-MSCA-IF-837491 ) from European Commission . ICA was supported by AECC predoctoral fellowship . NP was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovaci{\'o}n y Universidades , Gobierno de Espa{\~n}a ( FJC2019-042304-I ). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK , FCAECC and AIRC Accelerator Award Program (Project # C355/A26819 and # 22796 ). Funding Information: We would like to thank the staff of the flow cytometry core, the advances genomic lab, and the animal facility at CIMA Universidad de Navarra for their invaluable technical and intellectual assistance. We are particularly grateful to the healthy volunteers who donated bone marrow tissue for this study. We also acknowledge Ali O. Balubaid's help in writing. We would like to acknowledge Miguel Cocera-Fernandez's contribution to the Graphical Abstract. This research was funded by grants from The Spanish Government, through project PID2019-111192GA-I00 (MICINN) to DGC. Instituto de Salud Carlos III (ISCIII) and co-financed by FEDER: PI16/02024, PI17/00701 and PI19/01352, TRANSCAN EPICA AC16/00041, CIBERONC CB16/12/00489; Redes de Investigaci?n Cooperativa (TERCEL RD16/0011/0005); Spanish Ministry of Economy, Industry and Competitivity (RTHALMY SAF2017-92632-EXP); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Econ?mico y Empresarial (AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013). The study was also supported by Cancer Research UK [C355/A26819] and Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation (Brian van Novis), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III (ISCIII) (PI17/01346 and PI20/00152), co-funded by the ERDF (A way to make Europe); FC-AECC (AIO16163636SAEZ); Gobierno de Navarra (0011-3638-2020-000011) co-funded by the ERDF through the Operative Program 2014?2020 of Navarra and Gobierno de Navarra (0011-3597-2020-000005) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a, Sara Borrell award from Instituto de Salud Carlos III (ISCIII) and Marie Curie grant (H2020-MSCA-IF-837491) from European Commission. ICA was supported by AECC predoctoral fellowship. NP was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a (FJC2019-042304-I). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK, FCAECC and AIRC Accelerator Award Program (Project #C355/A26819 and #22796). B.S. J.T. F.P. and D.G.C. conceived and directed the research project. I.A.C. and B.S. designed the research experiments. I.A.C. with help from I.C. performed the isolation and FACS sorting of BM cells. J.Y. performed all the computational experiments, and analyzed the data with help from X.M.M. M.L. and N.P. A.V. performed the scRNA-Seq experiments. B.S. and D.G.C. supervised the work. All authors actively participated in the discussions underlying this manuscript. I.A.C. I.C. J.Y. B.S. and D.G.C. discussed the results and wrote the final manuscript with input from J.T. and F.P. All authors contributed to, read and approved the final manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = may,

day = "20",

doi = "10.1016/j.isci.2022.104225",

language = "English (US)",

volume = "25",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "5",

}

Ye, J, Calvo, IA, Cenzano, I, Vilas, A, Martinez-de-Morentin, X, Lasaga, M, Alignani, D, Paiva, B, Viñado, AC, San Martin-Uriz, P, Romero, JP, Quilez Agreda, D, Miñana Barrios, M, Sancho-González, I, Todisco, G, Malcovati, L, Planell, N, Saez, B, Tegner, JN, Prosper, F & Gomez-Cabrero, D 2022, 'Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation', iScience, vol. 25, no. 5, 104225. https://doi.org/10.1016/j.isci.2022.104225

TY - JOUR

T1 - Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

AU - Ye, Jin

AU - Calvo, Isabel A.

AU - Cenzano, Itziar

AU - Vilas, Amaia

AU - Martinez-de-Morentin, Xabier

AU - Lasaga, Miren

AU - Alignani, Diego

AU - Paiva, Bruno

AU - Viñado, Ana C.

AU - San Martin-Uriz, Patxi

AU - Romero, Juan P.

AU - Quilez Agreda, Delia

AU - Miñana Barrios, Marta

AU - Sancho-González, Ignacio

AU - Todisco, Gabriele

AU - Malcovati, Luca

AU - Planell, Nuria

AU - Saez, Borja

AU - Tegner, Jesper N.

AU - Prosper, Felipe

AU - Gomez-Cabrero, David

N1 - Funding Information: This research was funded by grants from The Spanish Government , through project PID2019-111192GA-I00 ( MICINN ) to DGC. Instituto de Salud Carlos III ( ISCIII ) and co-financed by FEDER : PI16/02024 , PI17/00701 and PI19/01352 , TRANSCAN EPICA AC16/00041 , CIBERONC CB16/12/00489 ; Redes de Investigación Cooperativa (TERCEL RD16/0011/0005 ); Spanish Ministry of Economy, Industry and Competitivity ( RTHALMY SAF2017-92632-EXP ); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Económico y Empresarial ( AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013 ). The study was also supported by Cancer Research UK [ C355/A26819 ] and Cancer Research UK , FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation ( Brian van Novis ), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III ( ISCIII ) ( PI17/01346 and PI20/00152 ), co-funded by the ERDF (A way to make Europe); FC-AECC ( AIO16163636SAEZ ); Gobierno de Navarra ( 0011-3638-2020-000011 ) co-funded by the ERDF through the Operative Program 2014–2020 of Navarra and Gobierno de Navarra ( 0011-3597-2020-000005 ) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovación y Universidades , Gobierno de España , Sara Borrell award from Instituto de Salud Carlos III ( ISCIII ) and Marie Curie grant ( H2020-MSCA-IF-837491 ) from European Commission . ICA was supported by AECC predoctoral fellowship . NP was supported by Juan de la Cierva grant from Ministerio de Ciencia , Innovación y Universidades , Gobierno de España ( FJC2019-042304-I ). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro ( AIRC ) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK , FCAECC and AIRC Accelerator Award Program (Project # C355/A26819 and # 22796 ). Funding Information: We would like to thank the staff of the flow cytometry core, the advances genomic lab, and the animal facility at CIMA Universidad de Navarra for their invaluable technical and intellectual assistance. We are particularly grateful to the healthy volunteers who donated bone marrow tissue for this study. We also acknowledge Ali O. Balubaid's help in writing. We would like to acknowledge Miguel Cocera-Fernandez's contribution to the Graphical Abstract. This research was funded by grants from The Spanish Government, through project PID2019-111192GA-I00 (MICINN) to DGC. Instituto de Salud Carlos III (ISCIII) and co-financed by FEDER: PI16/02024, PI17/00701 and PI19/01352, TRANSCAN EPICA AC16/00041, CIBERONC CB16/12/00489; Redes de Investigaci?n Cooperativa (TERCEL RD16/0011/0005); Spanish Ministry of Economy, Industry and Competitivity (RTHALMY SAF2017-92632-EXP); Departamento de Salud, Gobierno de Navarra 40/2016 and Departamento de Desarrollo Econ?mico y Empresarial (AGATA 0011-1411-2020-000010 and 0011-1411-2020-000013). The study was also supported by Cancer Research UK [C355/A26819] and Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program (EDITOR), the Multiple Myeloma Research Foundation Networks of excellence 2017 Immunotherapy Program Grant Award, the International Myeloma Foundation (Brian van Novis), and Paula and Rodger Riney Foundation to FP. Instituto de Salud Carlos III (ISCIII) (PI17/01346 and PI20/00152), co-funded by the ERDF (A way to make Europe); FC-AECC (AIO16163636SAEZ); Gobierno de Navarra (0011-3638-2020-000011) co-funded by the ERDF through the Operative Program 2014?2020 of Navarra and Gobierno de Navarra (0011-3597-2020-000005) to BS. G.T. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), 5x1000 Program (Project #21267). IC was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a, Sara Borrell award from Instituto de Salud Carlos III (ISCIII) and Marie Curie grant (H2020-MSCA-IF-837491) from European Commission. ICA was supported by AECC predoctoral fellowship. NP was supported by Juan de la Cierva grant from Ministerio de Ciencia, Innovaci?n y Universidades, Gobierno de Espa?a (FJC2019-042304-I). L.M. was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) 5x1000 Program (Project #21267) and Investigator Grant 2017 (Project #20125), and by Cancer Research UK, FCAECC and AIRC Accelerator Award Program (Project #C355/A26819 and #22796). B.S. J.T. F.P. and D.G.C. conceived and directed the research project. I.A.C. and B.S. designed the research experiments. I.A.C. with help from I.C. performed the isolation and FACS sorting of BM cells. J.Y. performed all the computational experiments, and analyzed the data with help from X.M.M. M.L. and N.P. A.V. performed the scRNA-Seq experiments. B.S. and D.G.C. supervised the work. All authors actively participated in the discussions underlying this manuscript. I.A.C. I.C. J.Y. B.S. and D.G.C. discussed the results and wrote the final manuscript with input from J.T. and F.P. All authors contributed to, read and approved the final manuscript. The authors declare no competing interests. Publisher Copyright: © 2022 The Authors

PY - 2022/5/20

Y1 - 2022/5/20

N2 - Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.

AB - Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.

KW - Biological sciences

KW - Omics

KW - Stem cells research

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85129539814&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2022.104225

DO - 10.1016/j.isci.2022.104225

M3 - Article

C2 - 35494238

AN - SCOPUS:85129539814

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 5

M1 - 104225

ER -

Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

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