Abstract
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A.Z and transcription factor PU.1 to key lymphoid fate regulator genes. Furthermore, Znhit1 deletion also abrogates H2A/H2A.Z exchange in MPPs. Thus Pcid2 controls lymphoid lineage commitment through the regulation of SRCAP remodelling activity.
Highlights
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion
multipotent progenitors (MPP), common myeloid progenitors (CMP) and common lymphoid progenitors (CLP) did not undergo apparent apoptosis in Pcid[2] KO vs. WT control mice (Fig. 2b). These results suggest that the skewed ratio of the CLPs and CMPs in Pcid[2] KO mice may be caused by lineage specification of the MPP progenitor
We found that Pcid2-deficient haematopoietic stem cells (HSC) transplantation caused declined bone marrow (BM) cellularity (Fig. 2h), as well as decreased numbers of MPPs and CMPs, but increased numbers of CLPs in the BM (Fig. 2i and Supplementary Fig. 3A)
Summary
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. How multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. In MPPs, Pcid[2] interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A.Z and transcription factor PU.[1] to key lymphoid fate regulator genes. Znhit[1] deletion abrogates H2A/H2A.Z exchange in MPPs. Pcid[2] controls lymphoid lineage commitment through the regulation of SRCAP remodelling activity. Through genome-scale RNA interference (RNAi) screening, Pcid[2] was identified to be an important factor that is involved in the self-renewal of mouse embryonic stem cells (ESCs)[13]. In the haematopoietic system, increased H2A.Z serves as a chromatin signature during the differentiation of haematopoietic stem or progenitor cells[24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
